Estimating Blood and Brain Concentrations and Blood-to-Brain Influx by Magnetic Resonance Imaging with Step-Down Infusion of Gd-DTPA in Focal Transient Cerebral Ischemia and Confirmation by Quantitative Autoradiography with Gd-[14C]DTPA

An intravenous step-down infusion procedure that maintained a constant gadolinium-diethylene-triaminepentaacetic acid (Gd-DTPA) blood concentration and magnetic resonance imaging (MRI) were used to localize and quantify the blood-brain barrier (BBB) opening in a rat model of transient cerebral ischemia ( n = 7). Blood-to-brain influx rate constant ( K i ) values of Gd-DTPA from such regions were estimated using MRI-Patlak plots and compared with the K, values of Gd-[ 14 C]DTPA, determined minutes later in the same rats with an identical step-down infusion, quantitative autoradiography (QAR), and single-time equation. The normalized plasma concentration-time integrals were identical for Gd-DTPA and Gd-[ 14 C]DTPA, indicating that the MRI protocol yielded reliable estimates of plasma Gd-DTPA levels. In six rats with a BBB opening, 14 spatially similar regions of extravascular Gd-DTPA enhancement and Gd-[ 14 C]DTPA leakage, including one very small area, were observed. The terminal tissue-plasma ratios of Gd-[ 14 C]DTPA tended to be slightly higher than those of Gd-DTPA in these regions, but the differences were not significant. The MRI-derived K i , values for Gd-DTPA closely agreed and correlated well with those obtained for Gd-[ 14 C]DTPA. In summary, MRI estimates of Gd-DTPA concentration in the plasma and brain and the influx rate are quantitatively and spatially accurate with step-down infusions.